scholarly journals An appeal to magic? The discovery of a non-enzymatic metabolism and its role in the origins of life

2018 ◽  
Vol 475 (16) ◽  
pp. 2577-2592 ◽  
Author(s):  
Markus Ralser
Keyword(s):  
Amino Acids ◽  
Metabolic Pathway ◽  
Metal Cation ◽  
Hydrogen Cyanide ◽  
Metabolic Pathways ◽  
Co2 Fixation ◽  
Enzymatic Reaction ◽  
Krebs Cycle ◽  
Pentose Phosphate ◽  
Long Time

Until recently, prebiotic precursors to metabolic pathways were not known. In parallel, chemistry achieved the synthesis of amino acids and nucleotides only in reaction sequences that do not resemble metabolic pathways, and by using condition step changes, incompatible with enzyme evolution. As a consequence, it was frequently assumed that the topological organisation of the metabolic pathway has formed in a Darwinian process. The situation changed with the discovery of a non-enzymatic glycolysis and pentose phosphate pathway. The suite of metabolism-like reactions is promoted by a metal cation, (Fe(II)), abundant in Archean sediment, and requires no condition step changes. Knowledge about metabolism-like reaction topologies has accumulated since, and supports non-enzymatic origins of gluconeogenesis, the S-adenosylmethionine pathway, the Krebs cycle, as well as CO2 fixation. It now feels that it is only a question of time until essential parts of metabolism can be replicated non-enzymatically. Here, I review the ‘accidents’ that led to the discovery of the non-enzymatic glycolysis, and on the example of a chemical network based on hydrogen cyanide, I provide reasoning why metabolism-like non-enzymatic reaction topologies may have been missed for a long time. Finally, I discuss that, on the basis of non-enzymatic metabolism-like networks, one can elaborate stepwise scenarios for the origin of metabolic pathways, a situation that increasingly renders the origins of metabolism a tangible problem.

scholarly journals Single amino acid-promoted reactions link a non-enzymatic chemical network to the early evolution of enzymatic pentose phosphate pathway

2020 ◽  
Author(s):  
Gabriel Piedrafita ◽  
Sreejith Varma ◽  
Cecilia Castro ◽  
Christoph Messner ◽  
Lukasz Szyrwiel ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Pentose Phosphate Pathway ◽  
Metabolic Pathways ◽  
Metal Ion ◽  
Enzymatic Reaction ◽  
Pentose Phosphate ◽  
Early Evolution ◽  
Environmental Chemical ◽  
Rna Backbone

AbstractHow metabolic pathways emerged in early evolution remains largely unknown. Recently discovered chemical networks driven by iron and sulfur resemble reaction sequences found within glycolysis, gluconeogenesis, the oxidative and reductive Krebs cycle, the Wood Ljungdahl as well as the S-adenosylmethionine pathways, components of the core cellular metabolic network. These findings suggest that the evolution of central metabolism was primed by environmental chemical reactions, implying that non-enzymatic reaction networks served as a “template” in the evolution of enzymatic activities. We speculated that the turning point for this transition would depend on the catalytic properties of the simplest structural components of proteins, single amino acids. Here, we systematically combine constituents of Fe(II)-driven non-enzymatic reactions resembling glycolysis and pentose phosphate pathway (PPP), with single proteinogenic amino acids. Multiple reaction rates are enhanced by amino acids. In particular, cysteine is able to replace (and/or complement) the metal ion Fe(II) in driving the non-enzymatic formation of the RNA-backbone metabolite ribose 5-phosphate from 6-phosphogluconate, a rate-limiting reaction of the oxidative PPP. In the presence of both Fe(II) and cysteine, a complex is formed, enabling the non-enzymatic reaction to proceed at a wide range of temperatures. At mundane temperatures, this ‘minimal enzyme-like complex’ achieves a much higher specificity in the formation of ribose 5-phosphate than the Fe(II)-driven reaction at high temperatures. Hence, simple amino acids can accelerate key steps within metal-promoted metabolism-like chemical networks. Our results imply a stepwise scenario, in which environmental chemical networks served as primers in the early evolution of the metabolic network structure.Significance StatementThe evolutionary roots of metabolic pathways are barely understood. Here we show results consistent with a stepwise scenario during the evolution of (enzymatic) metabolism, starting from non-enzymatic chemical networks. By systematic screening of metabolic-like reactivities in vitro, and using high-throughput analytical techniques, we identify an iron/cysteine complex to act as a ‘minimal enzymelike complex’, which consists of a metal ion, an amino acid, and a sugar phosphate ligand. Integrated in a metal-driven, non-enzymatic pentose phosphate pathway, it promotes the formation of the RNA-backbone precursor ribose 5-phosphate at ambient temperature.

Three new components contained in the vitelline coat of Tegula pfeifferi

Zygote ◽  
1999 ◽  
Vol 8 (S1) ◽  
pp. S61-S61 ◽  
Author(s):  
Kazu Haino-Fukushima ◽  
Xuxi Fan ◽  
Shouka Nakamura
Keyword(s):  
Amino Acids ◽  
Polyacrylamide Gel Electrophoresis ◽  
Enzymatic Reaction ◽  
Base Pairs ◽  
Sulphated Polysaccharides ◽  
Reading Frame ◽  
Glycosylation Sites ◽  
Long Time ◽  
Protein Components ◽  
Vitelline Coat

The vitelline coat (VC) lysin of Tegula, a marine molluscan genus, is released from the acrosome of sperm during fertilisation and can lyse the VC of only the same species. The lytic action of this lysin against the VC is not an enzymatic reaction, but a stoichiometric and irreversible one (Haino-Fukushima, 1974).The VC of Tegula pfeifferi consists of glycoproteins containing sulphated polysaccharides, which account for roughly two-thirds of the entire weight of the VC. The presence of a large quantity of polysaccharides in the VC had prevented rapid progress in the analysis of its protein components. Last year, we succeeded in a complete solubilisation of the VC by boiling for a long time in 1% SDS solution, and determined the cDNA sequence coding for a mature 41 kDa glycoprotein, which appears to be the major component of the VC from the results of SDS-polyacrylamide gel electrophoresis (PAGE). The cDNA, referred to as vcp41, comprises 1072 base pairs and contains one open reading frame with a sequence for 319 amino acids containing 19 amino acids of a signal peptide. The deduced amino acid sequence has five N-glycosylation sites and ten cysteine residues. It seems that almost 7 kDa in this 41kDa glycoprotein is polysaccharide constituents (Fan & Haino-Fukushima, 1998).

scholarly journals Improved workflow for mass spectrometry–based metabolomics analysis of the heart

2020 ◽  
Vol 295 (9) ◽  
pp. 2676-2686 ◽  
Author(s):  
Douglas A. Andres ◽  
Lyndsay E. A. Young ◽  
Sudhakar Veeranki ◽  
Tara R. Hawkinson ◽  
Bryana M. Levitan ◽  
...  
Keyword(s):  
Amino Acids ◽  
Krebs Cycle ◽  
Fold Increase ◽  
Glycogen Metabolism ◽  
Pentose Phosphate ◽  
Mouse Heart ◽  
Heart Metabolism ◽  
Adenosine Nucleotide ◽  
Metabolite Abundance

MS-based metabolomics methods are powerful techniques to map the complex and interconnected metabolic pathways of the heart; however, normalization of metabolite abundance to sample input in heart tissues remains a technical challenge. Herein, we describe an improved GC-MS–based metabolomics workflow that uses insoluble protein–derived glutamate for the normalization of metabolites within each sample and includes normalization to protein-derived amino acids to reduce biological variation and detect small metabolic changes. Moreover, glycogen is measured within the metabolomics workflow. We applied this workflow to study heart metabolism by first comparing two different methods of heart removal: the Langendorff heart method (reverse aortic perfusion) and in situ freezing of mouse heart with a modified tissue freeze-clamp approach. We then used the in situ freezing method to study the effects of acute β-adrenergic receptor stimulation (through isoproterenol (ISO) treatment) on heart metabolism. Using our workflow and within minutes, ISO reduced the levels of metabolites involved in glycogen metabolism, glycolysis, and the Krebs cycle, but the levels of pentose phosphate pathway metabolites and of many free amino acids remained unchanged. This observation was coupled to a 6-fold increase in phosphorylated adenosine nucleotide abundance. These results support the notion that ISO acutely accelerates oxidative metabolism of glucose to meet the ATP demand required to support increased heart rate and cardiac output. In summary, our MS-based metabolomics workflow enables improved quantification of cardiac metabolites and may also be compatible with other methods such as LC or capillary electrophoresis.

scholarly journals THE USE OF ILLUSTRATION IN BIOCHEMISTRY TEACHING AND LEARNING

2020 ◽  
Vol 21 (1) ◽  
pp. 142-149
Author(s):  
AZILA ADNAN
Keyword(s):  
Metabolic Pathway ◽  
Metabolic Pathways ◽  
Teaching And Learning ◽  
Learning Experience ◽  
Krebs Cycle ◽  
The Other ◽  
Food Science ◽  
Transport Chain ◽  
Strongly Agree ◽  
Interest And Motivation

Biochemistry is known as a complex course, especially the metabolic pathway topics. The main issue that instigate this initiative is the learners’ difficulty in understanding metabolic pathway topic(s), resulting in uninteresting learning environment. Hence, ‘the metabolic town’ illustration, that depicts three metabolic pathways (glycolysis, Krebs cycle, and electron transport chain) is used as an initiative to revive learners’ enthusiasm, which could breed interest and motivation to study this course. Trials were conducted with 35 students of Crop Science learners from the Faculty of Fisheries and Food Science, Universiti Malaysia Terengganu. Eighty-six percent (86.2%) responded ‘strongly agree’ and 13.8% responded ‘agree’ that the overall learning experience through the use of this illustration has created a positive and fun environment. Additionally, around 79% learners responded ‘strongly agree’ that their knowledge on these topics have improved while 17.2% responded ‘agree’. Nearly 100% of the learners agreed thus establish the connection between the lecture notes and the illustration. Other than that, from an intrinsic aspect, 72.4% of learners firmly agreed that this illustration aided their interest and motivation towards Biochemistry subject; while the other 27.6% agreed. 89.6% who answered strongly agreed showed that they are in favor of the use of illustration for revision while the rest agreed. Consequently, 86.2% of learners strongly agreed that the illustration boosted their understanding and boost their imagination, and the other 13.8% ‘agreed’. This study investigates how an illustration of analogy could improve the learning process.

scholarly journals Prebiotic Synthesis of α-Amino Acids and Orotate from α-Ketoacids Potentiates Transition to Extant Metabolic Pathways

2021 ◽  
Author(s):  
Ramanarayanan Krishnamurthy ◽  
Sunil Pulletikurti ◽  
Mahipal Yadav ◽  
Greg Springsteen
Keyword(s):  
Amino Acids ◽  
Metabolic Pathways ◽  
Prebiotic Chemistry ◽  
Krebs Cycle ◽  
Prebiotic Synthesis ◽  
Biological Pathways ◽  
Subsequent Evolution ◽  
Simultaneous Formation ◽  
Strecker Reaction ◽  
Seamless Transition

Abstract The Strecker reaction of aldehydes is the preeminent pathway to explain the prebiotic origins of a-amino acids. However, biology employs transamination of a-ketoacids to give rise to amino acids which are then transformed to nucleobases, implying subsequent evolution of the biosynthetic pathways – abiotically or biotically. Herein, we show that a-ketoacids react with cyanide and ammonia sources to form the corresponding a-amino acids – via the Bucherer-Bergs pathway. An efficient prebiotic transformation of oxaloacetate to aspartate via N-carbamoyl aspartate enables the simultaneous formation of dihydroorotate, paralleling the biochemical synthesis of orotate as the precursor to pyrimidine nucleobases. Glyoxylate forms both glycine and orotate, and reacts with malonate and urea to form aspartate and dihydroorotate. These results, along with the previously demonstrated protometabolic analogs of the Krebs cycle suggest that there can be a natural emergence of congruent forerunners of biological pathways with the potential for seamless transition from prebiotic chemistry to modern metabolism.

scholarly journals A cyanosulfidic origin of the Krebs cycle

2021 ◽  
Vol 7 (33) ◽  
pp. eabh3981
Author(s):  
Dougal J. Ritson
Keyword(s):  
Amino Acids ◽  
Hydrogen Cyanide ◽  
Present Report ◽  
Krebs Cycle ◽  
Glyoxylate Shunt ◽  
Uv Photolysis ◽  
Succinate Semialdehyde ◽  
Almost All

The centrality of the Krebs cycle in metabolism has long been interpreted as evidence of its antiquity, and consequently, questions regarding its provenance, and whether it initially functioned as a cycle or not, have received much attention. The present report shows that prebiotic oxidation of α-hydroxy carboxylates can be achieved by UV photolysis of a simple geochemical species (HS−), which leads to α-oxo carboxylates that feature in the Krebs cycle and glyoxylate shunt. Further reaction of these products leads to almost all intermediates of the Krebs cycle proper, succinate semialdehyde bypass, and glyoxylate shunt. Fumarate, the missing Krebs cycle component, and the required α-hydroxy carboxylates can be provided by a highly related hydrogen cyanide chemistry, which also provides precursors for amino acids, nucleotides, and phospholipids.

Hydrogen Cyanide Polymers from the Impact of Comet P/Shoemaker-Levy 9 on Jupiter

1997 ◽  
Vol 161 ◽  
pp. 179-187
Author(s):  
Clifford N. Matthews ◽  
Rose A. Pesce-Rodriguez ◽  
Shirley A. Liebman
Keyword(s):  
Amino Acids ◽  
Solar System ◽  
Hydrogen Cyanide ◽  
Nitrogen Heterocycles ◽  
Laboratory Studies ◽  
Heterogeneous Solids ◽  
The Many ◽  
Comet Halley ◽  
The Impact ◽  
By Products

AbstractHydrogen cyanide polymers – heterogeneous solids ranging in color from yellow to orange to brown to black – may be among the organic macromolecules most readily formed within the Solar System. The non-volatile black crust of comet Halley, for example, as well as the extensive orangebrown streaks in the atmosphere of Jupiter, might consist largely of such polymers synthesized from HCN formed by photolysis of methane and ammonia, the color observed depending on the concentration of HCN involved. Laboratory studies of these ubiquitous compounds point to the presence of polyamidine structures synthesized directly from hydrogen cyanide. These would be converted by water to polypeptides which can be further hydrolyzed to α-amino acids. Black polymers and multimers with conjugated ladder structures derived from HCN could also be formed and might well be the source of the many nitrogen heterocycles, adenine included, observed after pyrolysis. The dark brown color arising from the impacts of comet P/Shoemaker-Levy 9 on Jupiter might therefore be mainly caused by the presence of HCN polymers, whether originally present, deposited by the impactor or synthesized directly from HCN. Spectroscopic detection of these predicted macromolecules and their hydrolytic and pyrolytic by-products would strengthen significantly the hypothesis that cyanide polymerization is a preferred pathway for prebiotic and extraterrestrial chemistry.

Synthesis and Breakdown of the Universal Precursors to Biological Metabolism Promoted by Ferrous Iron

2018 ◽  
Author(s):  
Kamila B. Muchowska ◽  
Sreejith Jayasree VARMA ◽  
Joseph Moran
Keyword(s):  
Amino Acids ◽  
Chemical Reaction ◽  
Metabolic Pathways ◽  
Ferrous Iron ◽  
Reaction Network ◽  
Tca Cycle ◽  
Chemical Reaction Network ◽  
Metabolic Precursors ◽  
Tca Cycle Intermediates

How core biological metabolism initiated and why it uses the intermediates, reactions and pathways that it does remains unclear. Life builds its molecules from CO<sub>2 </sub>and breaks them down to CO<sub>2 </sub>again through the intermediacy of just five metabolites that act as the hubs of biochemistry. Here, we describe a purely chemical reaction network promoted by Fe<sup>2+ </sup>in which aqueous pyruvate and glyoxylate, two products of abiotic CO<sub>2 </sub>reduction, build up nine of the eleven TCA cycle intermediates, including all five universal metabolic precursors. The intermediates simultaneously break down to CO<sub>2 </sub>in a life-like regime resembling biological anabolism and catabolism. Introduction of hydroxylamine and Fe<sup>0 </sup>produces four biological amino acids. The network significantly overlaps the TCA/rTCA and glyoxylate cycles and may represent a prebiotic precursor to these core metabolic pathways.

scholarly journals Formaldehyde and De/Methylation in Age-Related Cognitive Impairment

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 913
Author(s):  
Ting Li ◽  
Yan Wei ◽  
Meihua Qu ◽  
Lixian Mou ◽  
Junye Miao ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cell Proliferation ◽  
Cognitive Impairment ◽  
Metabolic Pathways ◽  
Memory Formation ◽  
Epigenetic Alterations ◽  
Diagnostic Biomarker ◽  
Reactive Substance ◽  
Age Related ◽  
Novel Therapeutic

Formaldehyde (FA) is a highly reactive substance that is ubiquitous in the environment and is usually considered as a pollutant. In the human body, FA is a product of various metabolic pathways and participates in one-carbon cycle, which provides carbon for the synthesis and modification of bio-compounds, such as DNA, RNA, and amino acids. Endogenous FA plays a role in epigenetic regulation, especially in the methylation and demethylation of DNA, histones, and RNA. Recently, epigenetic alterations associated with FA dysmetabolism have been considered as one of the important features in age-related cognitive impairment (ARCI), suggesting the potential of using FA as a diagnostic biomarker of ARCI. Notably, FA plays multifaceted roles, and, at certain concentrations, it promotes cell proliferation, enhances memory formation, and elongates life span, effects that could also be involved in the aetiology of ARCI. Further investigation of and the regulation of the epigenetics landscape may provide new insights about the aetiology of ARCI and provide novel therapeutic targets.

Sign in / Sign up

Export Citation Format

Share Document